A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model

Xiaonan Tan, Gyeungyun Kim, Dahee Lee, Jungju Oh, Minkyung Kim, Chunxian Piao, Jaewon Lee, Min Sang Lee, Ji Hoon Jeong, Minhyung Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR-21), which inhibits the expression of pro-apoptotic genes such as phosphatase and tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic effects for glioblastomas. In this study, curcumin was loaded into deoxycholic acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle (DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and miR21ASO. Gel retardation and heparin competition assays showed that DP-Cur formed stable complexes with miR21ASO. The anti-tumor effects of the combined delivery of curcumin and miR21ASO were evaluated in C6 glioblastoma cells. In vitro transfection showed that DP-Cur had an miR21ASO delivery efficiency similar to that of polyethylenimine (25 kDa, PEI25k) and DP. In the C6 cells, the delivery of miR21ASO using DP-Cur effectively reduced the miR21 level. The miR21ASO/DP-Cur complex induced apoptosis more effectively than the single delivery of curcumin or miR21ASO. The therapeutic effect of the miR21ASO/DP-Cur complex was also evaluated in an intracranial glioblastoma animal model. The miR21ASO/DP-Cur complex reduced the tumor volume more effectively than single therapy of curcumin or miR21ASO. Immunohistochemistry showed that PDCD4 and PTEN were induced in the miR21ASO/DP and miR21ASO/DP-Cur complex groups. Therefore, DP-Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and curcumin may be useful in the development of combination therapy for glioblastoma.

Original languageEnglish
Pages (from-to)407-417
Number of pages11
JournalBiomaterials Science
Volume6
Issue number2
DOIs
StatePublished - 2018 Feb 1

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Curcumin
Antisense Oligonucleotides
Oligonucleotides
Micelles
Cell death
MicroRNAs
Tumors
Animals
Phosphatases
Polyethyleneimine
Assays
Phosphoric Monoester Hydrolases
Brain
Gels
Genes
Acids
Deoxycholic Acid
Heparin
Apoptosis

Cite this

Tan, Xiaonan ; Kim, Gyeungyun ; Lee, Dahee ; Oh, Jungju ; Kim, Minkyung ; Piao, Chunxian ; Lee, Jaewon ; Lee, Min Sang ; Jeong, Ji Hoon ; Lee, Minhyung. / A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model. In: Biomaterials Science. 2018 ; Vol. 6, No. 2. pp. 407-417.
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A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model. / Tan, Xiaonan; Kim, Gyeungyun; Lee, Dahee; Oh, Jungju; Kim, Minkyung; Piao, Chunxian; Lee, Jaewon; Lee, Min Sang; Jeong, Ji Hoon; Lee, Minhyung.

In: Biomaterials Science, Vol. 6, No. 2, 01.02.2018, p. 407-417.

Research output: Contribution to journalArticle

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T1 - A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model

AU - Tan, Xiaonan

AU - Kim, Gyeungyun

AU - Lee, Dahee

AU - Oh, Jungju

AU - Kim, Minkyung

AU - Piao, Chunxian

AU - Lee, Jaewon

AU - Lee, Min Sang

AU - Jeong, Ji Hoon

AU - Lee, Minhyung

PY - 2018/2/1

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AB - A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR-21), which inhibits the expression of pro-apoptotic genes such as phosphatase and tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic effects for glioblastomas. In this study, curcumin was loaded into deoxycholic acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle (DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and miR21ASO. Gel retardation and heparin competition assays showed that DP-Cur formed stable complexes with miR21ASO. The anti-tumor effects of the combined delivery of curcumin and miR21ASO were evaluated in C6 glioblastoma cells. In vitro transfection showed that DP-Cur had an miR21ASO delivery efficiency similar to that of polyethylenimine (25 kDa, PEI25k) and DP. In the C6 cells, the delivery of miR21ASO using DP-Cur effectively reduced the miR21 level. The miR21ASO/DP-Cur complex induced apoptosis more effectively than the single delivery of curcumin or miR21ASO. The therapeutic effect of the miR21ASO/DP-Cur complex was also evaluated in an intracranial glioblastoma animal model. The miR21ASO/DP-Cur complex reduced the tumor volume more effectively than single therapy of curcumin or miR21ASO. Immunohistochemistry showed that PDCD4 and PTEN were induced in the miR21ASO/DP and miR21ASO/DP-Cur complex groups. Therefore, DP-Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and curcumin may be useful in the development of combination therapy for glioblastoma.

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